Novel Mathematical Model Predicts New Wave Of Drug-resistant HIV Infections In San Francisco

A mathematical model shows that a new wave of drug-resistant HIV is
rising among among men in San Francisco who have sex with men and that
this trend will continue over the next few years, according to a new
study from the UCLA AIDS Institute. At the same time, the evolution of
drug-resistant HIV may have actually reduced the severity of the city's
epidemic, saving many men from becoming infected.

The model and its results were just unveiled by UCLA biomathematics
professor Sally Blower, director of the Biomedical Modeling Center at
the David Geffen School of Medicine at UCLA, during a session on
drug-resistant diseases at the annual American Association for the
Advancement of Science conference in Boston.

"Our amplification cascade model has been validated by our
reconstructions and can now be used to design novel and effective
health policies for controlling single-, dual- and triple-class
resistant strains of HIV in both resource-rich and resource-constrained
countries," said Blower, who is also a member of the UCLA AIDS
Institute.

The model enabled the researchers to reconstruct the epidemic's past
and predict its future by calculating the evolution of several classes
of drug-resistant HIV strains in San Francisco.

The research relied on a novel multi-strain mathematical model
called the Amplification Cascade Model to examine the rise between 1987
and 2007 of HIV strains resistant to the three major classes of drugs
-- nucleosides (NRTIs), nonnucleosides (NNRTIs) and protease inhibitors
(PIs). The model took into account three interacting processes --
transmitted, acquired and amplified resistance -- the last of which
refers to amplification of drug-resistant strains in HIV-positive
people due to the repeated use of multiple-treatment drug regimens.

The study tracked uninfected individuals; newly infected people in
the primary stage of infection; chronically infected individuals who
were not yet eligible for treatment; chronically infected people who
remained untreated, though eligible for it; and patients under
treatment.

Researchers found complex waves of rising and falling single-, dual-
and triple-class drug-resistant HIV strains over 20 years, with more
complex patterns continuing to evolve.

The model predicts that resistance to NRTIs will decline
substantially and PI resistance will fall slightly through 2012, and
that resistance to NNRTIs will rise over the next five years and then
begin falling.

Although strains with dual- and triple-class resistance will be
transmitted, they will be far less potent than wild-type HIV strains --
those strains that have not developed drug-resistant mutations and
remain sensitive to all classes of drugs.

Most surprising of all, the evolution of drug-resistant HIV strains
has substantially reduced the severity of the San Francisco AIDS
epidemic because the strains that have emerged have become less
infectious than the wild-type strains.

Other collaborators on this study were Erin Bodine of the University
of Tennessee, Jim Kahn of UC San Francisco, Justin T. Okano of UCLA and
Robert Smith of the University of Ottawa.

The National Institute of Allergy and Infectious Diseases funded this research.